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Aging Influences Multiple Indices Of Oxidative Stress In The Heart Of The Fischer 344/Nnia X Brown Norway/Binia Rat, Shinichi Asano

Theses, Dissertations and Capstones

Here we report the influence of aging on multiple markers of oxidativenitrosative stress in the heart of adult (6-month), aged (30-month) and very aged (36- month) Fischer 344/NNiaHSd X Brown Norway/BiNia (F344/NXBN) rats. Compared to 6 month old rat hearts, indices of oxidative (superoxide anion (–O2 ·), 4-hyrdoxy-2- nonenal (4-HNE)) and nitrosative (protein nitrotyrosylation) stress were 34.1 ± 28.1%, 186 ± 28.1% and 94 ± 5.8% higher, respectively, in 36-month hearts and these findings were highly correlated with increases in left ventricular wall thickness (r>0.669; r>0.710 and p<0.01, respectively). Regression analysis showed that increases in cardiac oxidative-nitrosative stress with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in transcriptional (NF-κB) activities, signaling (mitogen activated protein kinases along with Src), apoptotic ( Bcl-2, Traf-2), and cellular stress (HSPs). These results suggest that the aging F344/NXBN heart may be highly suited for unraveling the molecular events that lead to age-associated alterations in cardiac oxidative stress.